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Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease
Alcoholic liver disease (ALD) is one of the main causes of death in chronic liver disease. Oxidative stress and pyroptosis are important factors leading to ALD. Bromodomain-containing protein 4 (BRD4) is a factor that we have confirmed to regulate ALD. As a phenolic acid compound, sinapic acid (SA)...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212038/ https://www.ncbi.nlm.nih.gov/pubmed/34149421 http://dx.doi.org/10.3389/fphar.2021.668708 |
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author | Chu, Junyi Yan, Ran Wang, Sai Li, Guoyang Kang, Xiaohui Hu, Yan Lin, Musen Shan, Wen Zhao, Yan Wang, Zhecheng Sun, Ruimin Yao, Jihong Zhang, Ning |
author_facet | Chu, Junyi Yan, Ran Wang, Sai Li, Guoyang Kang, Xiaohui Hu, Yan Lin, Musen Shan, Wen Zhao, Yan Wang, Zhecheng Sun, Ruimin Yao, Jihong Zhang, Ning |
author_sort | Chu, Junyi |
collection | PubMed |
description | Alcoholic liver disease (ALD) is one of the main causes of death in chronic liver disease. Oxidative stress and pyroptosis are important factors leading to ALD. Bromodomain-containing protein 4 (BRD4) is a factor that we have confirmed to regulate ALD. As a phenolic acid compound, sinapic acid (SA) has significant effects in antioxidant, anti-inflammatory and liver protection. In this study, we explored whether SA regulates oxidative stress and pyroptosis through BRD4 to play a protective effect in ALD. Male C57BL/6 mice and AML-12 cells were used for experiments. We found that SA treatment largely abolished the up-regulation of BRD4 and key proteins of the canonical pyroptosis signalling in the liver of mice fed with alcohol, while conversely enhanced the antioxidant response. Consistantly, both SA pretreatment and BRD4 knockdown inhibited oxidative stress, pyroptosis, and liver cell damage in vitro. More importantly, the expression levels of BRD4 and pyroptosis indicators increased significantly in ALD patients. Molecule docking analysis revealed a potent binding of SA with BRD4. In conclusion, this study demonstrates that SA reduces ALD through BRD4, which is a valuable lead compound that prevents the ALD process. |
format | Online Article Text |
id | pubmed-8212038 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82120382021-06-19 Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease Chu, Junyi Yan, Ran Wang, Sai Li, Guoyang Kang, Xiaohui Hu, Yan Lin, Musen Shan, Wen Zhao, Yan Wang, Zhecheng Sun, Ruimin Yao, Jihong Zhang, Ning Front Pharmacol Pharmacology Alcoholic liver disease (ALD) is one of the main causes of death in chronic liver disease. Oxidative stress and pyroptosis are important factors leading to ALD. Bromodomain-containing protein 4 (BRD4) is a factor that we have confirmed to regulate ALD. As a phenolic acid compound, sinapic acid (SA) has significant effects in antioxidant, anti-inflammatory and liver protection. In this study, we explored whether SA regulates oxidative stress and pyroptosis through BRD4 to play a protective effect in ALD. Male C57BL/6 mice and AML-12 cells were used for experiments. We found that SA treatment largely abolished the up-regulation of BRD4 and key proteins of the canonical pyroptosis signalling in the liver of mice fed with alcohol, while conversely enhanced the antioxidant response. Consistantly, both SA pretreatment and BRD4 knockdown inhibited oxidative stress, pyroptosis, and liver cell damage in vitro. More importantly, the expression levels of BRD4 and pyroptosis indicators increased significantly in ALD patients. Molecule docking analysis revealed a potent binding of SA with BRD4. In conclusion, this study demonstrates that SA reduces ALD through BRD4, which is a valuable lead compound that prevents the ALD process. Frontiers Media S.A. 2021-06-04 /pmc/articles/PMC8212038/ /pubmed/34149421 http://dx.doi.org/10.3389/fphar.2021.668708 Text en Copyright © 2021 Chu, Yan, Wang, Li, Kang, Hu, Lin, Shan, Zhao, Wang, Sun, Yao and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Chu, Junyi Yan, Ran Wang, Sai Li, Guoyang Kang, Xiaohui Hu, Yan Lin, Musen Shan, Wen Zhao, Yan Wang, Zhecheng Sun, Ruimin Yao, Jihong Zhang, Ning Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease |
title | Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease |
title_full | Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease |
title_fullStr | Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease |
title_full_unstemmed | Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease |
title_short | Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease |
title_sort | sinapic acid reduces oxidative stress and pyroptosis via inhibition of brd4 in alcoholic liver disease |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212038/ https://www.ncbi.nlm.nih.gov/pubmed/34149421 http://dx.doi.org/10.3389/fphar.2021.668708 |
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